3D in vitro modelling of human patient microglia: A focus on clinical translation and drug development in neurodegenerative diseases

Abstract

Microglia have an increasingly well-recognised role in the pathogenesis of neurodegenerative diseases, thereby becoming attractive therapeutic targets. However, the development of microglia-targeted therapeutics for neurodegeneration has had limited success. This stems partly from the lack of clinically relevant microglia model systems. To circumvent this translational gap, patient-derived microglial cell models established using conventional 2D in vitro techniques have emerged. Though promising, these models lack the microenvironment and multicellular interactions of the brain needed to maintain microglial homeostasis. In this review, we discuss the use of 3D in vitro platforms to improve microglia modelling and their potential benefits to fast-track drug development for neurodegenerative diseases.

Keywords: 2D and 3D in vitro models; Disease biomarker discovery; Drug development; Microglia-targeted therapeutics; Monocyte-derived microglia; Neurodegenerative diseases.